This project has established a series of core neuro-biological findings regarding the basis of Conduct Disorder (CD), particularly CD with Callous-Unemotional traits (reduced guilt and empathy);CD+CU: (i) CD+CU is associated with impaired processing of the fear of others and this impairment is associated with a reduced response by the amygdala to these expressions. This impairment is specific to fearful expressions and not seen to angry expressions. These data allow us to understand the basis of the empathy deficit in patients with this disorder. (ii) CD+CU is associated with impaired decision making and this impairment is associated with disruption in the representation of reinforcement information (how likely the action is to result in reward/ punishment) within ventromedial prefrontal cortex. These data allow us to understand the basis of the decision making impairment in patients with this disorder. (iii) Patients with Attention Deficit Hyperactivity Disorder (ADHD) but without CD show no difficulties in either their amygdala response to fearful expressions or the signaling of reinforcement information within ventromedial prefrontal cortex. This is important because CD and ADHD are often seen in the same youth. About 65% of our youth with CD+CU also meet criteria for ADHD. However, by showing that youth with ADHD, but without CD, show no problems in fearful expression or reinforcement processing, we can be sure that these difficulties are linked to CD+CU rather than the comorbid ADHD. In studies either recently completed or currently on-going, we have extended our earlier work by showing that: (i) The empathy deficits in CD+CU extend to the response to another individuals pain. These deficits are also related to reduced amygdala responses to another individuals pain. (ii) The decision making impairments are not only associated with deficiencies in the representation of reinforcement information within ventromedial prefrontal cortex but also with deficiencies within ventromedial frontal cortex and the caudate with respect to prediction error signaling. Prediction error signaling occurs in the brain when the individual unexpectedly receives reward or punishment. This signaling is important as it prompts rapid learning of the association between actions that elicited this reinforcement and the reinforcement itself. Poor prediction error signaling means poorer emotional learning and consequently poorer decision making. (iii) In collaboration with Dr. Leibenluft, we have shown that while youth with CD+CU and childhood bipolar disorder behaviorally show some similarities in their decision making impairment, the neural basis of these impairments are markedly different. CD+CU is associated with difficulties in ventromedial prefrontal cortex and caudate functioning with respect to the representation of reinforcement information and prediction error signaling. Childhood bipolar disorder is not. Instead, childhood bipolar disorder is associated with difficulties in organizing regions of lateral frontal and parietal cortex important for attentional control. Youth with CD+CU show no impairment in these capacities. Importantly, our empirical work distinguishing youth with CD+CU from youth with ADHD and youth with bipolar disorder allows us to further specify a neurobiological account of youth with CD+CU that is specific to this disorder. Moreover, this work allows us to determine which neural regions are disrupted in CD+CU and thus provides clues with respect to interventions that might benefit youth with CD+CU. Critically, this work has allowed us to identify objective bio-markers that can be used to assess treatment efficacy in this population. Currently, my group is developing protocols investigating two treatment interventions in youth with CD+CU using the fMRI biomarker tasks identified within this protocol to assess treatment efficacy.